Cardiac biomarkers retain prognostic significance in patients with heart failure and chronic obstructive pulmonary disease.

AIMS: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2). METHODS: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values. RESULTS: Patients had a median age of 66 years (interquartile interval 57-74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487-2725), 17 ng/l (9-31) and 30 ng/ml (22-44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P < 0.001), but not sST2 (P = 0.165). Over a median 2.0-year follow-up (1.5-2.5), 1717 patients (21%) died, and 1298 (16%) died from cardiovascular causes; 2255 patients (28%) were hospitalized for HF over 1.8 years (0.9-2.1). NT-proBNP, hs-TnT and sST2 predicted the three end points regardless of COPD status. The best cut-offs from receiver-operating characteristics analysis were higher in patients with COPD than in those without. Patients with all three biomarkers higher than or equal to end-point- and COPD-status-specific cut-offs were also those with the worst prognosis. CONCLUSIONS: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.

Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

Impact of change in iron status over time on clinical outcomes in heart failure according to ejection fraction phenotype.

AIMS: The importance of iron deficiency (ID) in heart failure with preserved ejection fraction (HFpEF) is unknown. In HF with reduced ejection fraction (HFrEF), ID is reported as an independent predictor of mortality in HF although not all published studies agree. Different definitions of ID have been assessed, and the natural history of untreated ID not established, which may explain the conflicting results. This study aimed to assess the relationship between ID and mortality in HFpEF, clarify which definition of ID correlates best with outcomes in HFrEF, and determine the prognostic importance of change in ID status over time. METHODS AND RESULTS: Analyses were conducted on data from 1563 patients participating in a prospective international cohort study comparing HFpEF with HFrEF. Plasma samples from baseline and 6 month visits were analysed for the presence of ID. Two ID definitions were evaluated: IDFerritin  = 'ferritin < 100 mcg/L or ferritin 100-300 mcg/L + transferrin saturation < 20%' and IDTsat  = 'transferrin saturation < 20%'. The risk of all-cause mortality and death/HF hospitalization associated with baseline ID (IDFerritin or IDTsat ) and change in ID status at 6 months (persistent, resolving, developing, or never present) was estimated in multivariable Cox proportional hazards models. Of 1563 patients, 1115 (71%) had HFrEF and 448 (29%) HFpEF. Prevalence of ID was similar in HFpEF and HFrEF (58%). Patients with ID were more likely to be female, diabetic, and have a higher co-morbid burden than patients without ID. ID by either definition did not confer independent risk for either all-cause mortality or death/HF hospitalization for patients with HFpEF [IDFerritin hazard ratio (HR) 0.65 (95% confidence interval 0.40-1.05), P = 0.08; IDTsat HR 1.16 (0.72-1.87), P = 0.55]. In the overall study cohort (HFrEF + HFpEF) and HFrEF subgroup, IDFerritin was inferior to IDTsat in prediction of all-cause mortality [overall cohort: HR 1.21 (0.95-1.53), P = 0.12 vs. HR 1.95 (1.52-2.51), P < 0.01; HFrEF: HR 1.12 (0.85-1.48), P = 0.43 vs. HR 1.57 (1.15-2.14), P < 0.01]. Persistence of IDTsat at 6 months was strongly associated with poor outcomes compared with never having IDTsat [HR 2.22 (1.42-3.46), P < 0.01] or having IDTsat at baseline self-resolve by 6 months [HR 1.40 (1.06-1.86), P = 0.02]. CONCLUSIONS: Iron deficiency is equally prevalent in HFpEF and HFrEF but is negatively prognostic only in HFrEF. The natural history of ID is important; persistent ID is strongly associated with mortality whereas resolution is not. IDTsat is the superior definition of ID and should inform future trials investigating the efficacy of intravenous iron replacement in patients with HFrEF.

Ethnic differences in atrial fibrillation in patients with heart failure from Asia-Pacific.

OBJECTIVE: Ethnic differences in the prevalence of atrial fibrillation (AF) in heart failure (HF) remain unclear. We compared the prevalence and clinical correlates of AF among different ethnicities in an Asian-Pacific population with HF. METHODS: Patients with validated HF were prospectively studied across Singapore and New Zealand (NZ). RESULTS: Among 1746 patients with HF (62% Asian, 26% women, mean age 66 (SD 13) years, mean ejection fraction (EF) 37 (SD 16%), 39% had AF. The prevalence of AF was markedly lower in Singapore-Asians than NZ-Europeans (24% vs 63%; p<0.001), even after adjusting for age, clinical and echocardiographic covariates, regardless of EF group (pinteraction for EF=0.39). Patients with AF were older, had higher body mass index and were more likely to have a history of hypertension, stroke, peripheral vascular disease, renal disease, chronic respiratory disease and increased alcohol intake, but less likely to have diabetes. Clinical correlates were similar for Asians and NZ-Europeans, except diabetes: Asian diabetic patients with HF had less AF compared with Asian patients without diabetes (OR 0.66, 95% CI 0.50 to 0.88), whereas among NZ-Europeans there was no significant association between diabetes and AF (OR 1.22, 95% CI 0.85 to 1.75) (pinteraction for ethnicity=0.01). AF was associated with a higher crude composite outcome of mortality and HF hospitalisations at 2 years (HR 1.19, 95% CI 1.02 to 1.38). CONCLUSION: There is a strikingly lower prevalence of AF among Asian compared with NZ-European patients with HF. The underlying mechanisms for the lower prevalence of AF among Asians, particularly in the presence of diabetes, deserve further study. TRIAL REGISTRATION NUMBER: ACTRN12610000374066.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

Aims: Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Methods and results: Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. Conclusion: These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Trial Registration: Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

N-terminal pro-B-type natriuretic peptide and prognosis in Caucasian vs. Asian patients with heart failure.

AIMS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the most frequently used biomarker in heart failure (HF), but its prognostic utility across ethnicities is unclear. METHODS AND RESULTS: This study included 546 Caucasians with HF from the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure and 578 Asians with HF from the Singapore Heart Failure Outcomes and Phenotypes study. NT-proBNP was measured at discharge after HF hospitalization. The studied outcome was a composite of all-cause mortality and HF hospitalization at 18 months. Compared with Caucasian patients, Asian patients were younger (63 ± 12 vs. 71 ± 11 years); less often female (26% vs. 39%); and had lower body mass index (26 vs. 27 kg/m2 ), better renal function (61 ± 37 vs. 54 ± 20 mL/min/1.73 m2 ), lower rates of atrial fibrillation (25% vs. 46%), strikingly higher rates of diabetes (59% vs. 30%), and higher rates of hypertension (76% vs. 44%). Despite these clear inter-group differences in individual drivers of NT-proBNP, average levels were similar in Asians [2709 (1350, 6302) pg/mL] and Caucasians [2545 (1308, 5484) pg/mL] (P = 0.514). NT-proBNP was strongly associated with outcome [hazard ratio 1.28 (per doubling), 95% confidence interval 1.18-1.39, P < 0.001], regardless of ethnicity (Pinteraction  = 0.719). NT-proBNP was similarly associated with outcome in HF with reduced and preserved ejection fraction in Asian (Pinteraction  = 0.776) and Caucasian patients (Pinteraction  = 0.558). CONCLUSIONS: NT-proBNP has similar prognostic performance in Asians and Caucasians with HF despite ethnic differences in known clinical determinants of plasma NT-proBNP.

Single-dose intravenous iron in Southeast Asian heart failure patients: A pilot randomized placebo-controlled study (PRACTICE-ASIA-HF).

AIMS: Iron deficiency is highly prevalent in Southeast Asians with heart failure (HF) and associated with worse outcomes. This trial aimed to assess the effect of intravenous iron in Southeast Asians hospitalized with decompensated HF. METHODS AND RESULTS: Fifty patients hospitalized for acute decompensated HF, regardless of ejection fraction, with iron deficiency (defined as serum ferritin <300 ng/mL if transferrin saturation is <20%) were randomized to receive either one dose of intravenous ferric carboxymaltose (FCM) 1000 mg or placebo (0.9% saline) following HF stabilization and before discharge in two Singapore tertiary centres. The primary endpoint was difference in 6-min walk test (6MWT) distance over 12 weeks, while secondary endpoints were quality of life assessed using validated Kansas City Cardiomyopathy Questionnaire (KCCQ) and Visual Analogue Scale (VAS). Improvement in 6MWT distance at Week 12 was observed in both FCM and placebo groups (from 252 ± 123 to 334 ± 128 m and from 243 ± 67 to 301 ± 83 m, respectively). Unadjusted analysis showed 6MWT distance for FCM exceeded that for placebo, but adjustment for baseline covariates and time attenuated this effect {adjusted mean difference between groups: 0.88 m [95% confidence interval (CI) -30.2 to 32.0, P = 0.956]}. KCCQ overall summary and VAS were similar in both groups [adjusted mean difference: KCCQ -1.48 (95% CI -8.27 to 5.31, P = 0.670) and VAS 0.26 (95% CI -0.33 to 0.86, P = 0.386)]. FCM was well tolerated with no serious treatment-related adverse events. CONCLUSIONS: Intravenous FCM administered pre-discharge in Southeast Asians hospitalized with decompensated HF is clinically feasible. Changes in 6MWT distance should be measured beyond Week 12 to account for background therapy effects.

Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure.

OBJECTIVES: The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND: Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the world's diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS: Two contemporary population-based HF cohorts were combined: from Singapore (n = 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n = 19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS: Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p < 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45; 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; pinteraction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; pinteraction = 0.045). CONCLUSIONS: Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications.

Rationale and design of a pilot randomized controlled trial to assess the role of intravenous ferric carboxymaltose in Asian patients with heart failure (PRACTICE-ASIA-HF).

AIMS: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) worldwide regardless of haemoglobin levels. Results from therapeutic trials of intermittently dosed intravenous (i.v.) iron are promising in the ambulatory Caucasian population with HF with reduced left ventricular ejection fraction, although evidence is scarce in Asia. The Pilot Randomized Controlled Trial to Assess the Role of Intravenous Ferric Carboxymaltose in Asian Patients with Heart Failure aims to assess the effect of single-dose i.v. ferric carboxymaltose (FCM) in a multi-ethnic Asian population with HF and ID. METHODS AND RESULTS: This is an open-label, randomized, placebo-controlled trial recruiting stabilized inpatients with decompensated HF (regardless of left ventricular ejection fraction), ID [defined as serum ferritin <300 ng/mL if transferrin saturation <20%] and haemoglobin ≤14 g/dL. Patients from two tertiary institutions were randomized in a 1:1 ratio to receive a single dose of either i.v. FCM (Ferinject®) 1000 mg or i.v. normal saline. The primary endpoint is the change in 6-min walk distance at Weeks 4 and 12, and secondary endpoints are changes at Weeks 4 and 12 in (i) quality of life as measured by the Kansas City Cardiomyopathy Questionnaire and Visual Analogue Scale scores and (ii) New York Heart Association functional class. CONCLUSIONS: Preliminary efficacy data on i.v. FCM therapy in Asian HF are expected from this pilot study to support larger-scale multicentre therapeutic i.v. FCM trials within Asia.

Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction.

AIM: Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N-terminal pro-brain natriuretic peptide (NT-proBNP), an indicator of haemodynamic wall stress. METHODS: Plasma GDF15 and NT-proBNP were prospectively measured in 916 consecutive patients with HFrEF (EF <50%; n = 730) and HFpEF (EF ≥50%; n = 186), and measured again at 6 months in 488 patients. Patients were followed up for a composite outcome of death or first HF rehospitalization. RESULTS: Median GDF15baseline values were similarly elevated in HFpEF [2862 (1812 represent the 25th percentile and 4176 represent the 75th percentile) ng/L] and HFrEF [2517 (1555, 4030) ng/L] (P = 0.184), whereas NT-proBNP was significantly lower in HFpEF than HFrEF (1119 ng/L vs. 2335 ng/L, P < 0.001). Independent correlates of GDF15baseline were age, systolic blood pressure, New York Heart Association (NYHA) class, diabetes, atrial fibrillation, sodium, haemoglobin, creatinine, diuretic therapy, high sensitivity troponin T (hsTnT) and NT-proBNP (all P < 0.05). During a median follow-up of 23 months, there were 379 events (307 HFrEF, 72 HFpEF). GDF15 remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors including hsTnT and NT-proBNP (adjusted hazard ratio 1.76 per 1 Ln U, 95% confidence interval 1.39-2.21; P < 0.001), regardless of HF group (Pinteraction = 0.275). GDF15baseline provided incremental prognostic value when added to clinical predictors, hsTnT and NT-proBNP (area under receiver operating characteristic curve increased from 0.720 to 0.740, P < 0.019), with a net reclassification improvement of 0.183 (P = 0.004). Patients with ≥20% GDF156months increase had higher risk for composite outcome (adjusted hazard ratio 1.68, 95% confidence interval 1.15-2.45; P = 0.007) compared with those with GDF156months within ± 20% of baseline. CONCLUSIONS: The similarly elevated levels and independent prognostic utility of GDF15 in HFrEF and HFpEF suggest that beyond haemodynamic stress (NT-proBNP), inflammatory injury (GDF15) may play an important role in both HF syndromes.

Reverse Remodeling and Prognosis Following Kidney Transplantation in Contemporary Patients With Cardiac Dysfunction.

BACKGROUND: Cardiac dysfunction influences candidate selection for kidney transplantation. There is a paucity of data regarding predictors of myocardial recovery following kidney transplantation and long-term outcomes. OBJECTIVES: The purpose of this study was to identify the extent of reverse remodeling in our kidney transplant population and the predictors of such changes, and to assess outcomes in these patients. METHODS: We reviewed 232 patients who underwent kidney transplantation at the Cleveland Clinic from 2003 to 2013 and who had baseline and post-transplant echocardiograms; patients with simultaneous heart transplantation were excluded. RESULTS: Post-transplantation mean left ventricular ejection fraction (LVEF) improved in those with LV dysfunction (increased from 41% to 50%; p < 0.0001; n = 66). There was significant improvement in other parameters, including diastolic function, LV end-diastolic dimension, LV mass, and right ventricular systolic pressure. After adjusting for multiple clinical variables, increased hemoglobin following transplantation was associated with an improved LVEF (odds ratio: 1.50; 95% confidence interval [CI]: 1.07 to 2.14; p = 0.016) and reduced mortality (hazard ratio [HR]: 0.65; 95% CI: 0.49 to 0.87; p = 0.004). An improved LVEF ≥10% predicted survival independently of a pre-transplantation LVEF (HR: 0.46; 95% CI: 0.21 to 0.93; p = 0.031). CONCLUSIONS: Kidney transplantation is associated with improved cardiac structure and function. A rise in post-transplantation hemoglobin was a significant factor associated with such changes, in addition to conferring a survival advantage.

Iron deficiency in a multi-ethnic Asian population with and without heart failure: prevalence, clinical correlates, functional significance and prognosis.

AIMS: Current heart failure (HF) guidelines highlight the importance of iron deficiency (ID) in HF. Whether HF itself or age-related comorbidities contribute to ID is uncertain, and previous data were limited to Western populations. We aimed to study the prevalence, clinical correlates, functional significance and prognosis of ID in HF patients, compared with community-based controls in a multi-ethnic Southeast Asian population. METHODS AND RESULTS: Iron status was assessed in 751 HF patients (age 62.0 ± 12.2 years, 75.5% men, 64.7% Chinese, 23.9% Malay, 10.2% Indian) and 601 controls (age 56.9 ± 10.4 years, 49.8% men, 70.9% Chinese, 21.5% Malay, 7.2% Indian). ID, defined as ferritin <100 µg/L or ferritin 100-300 µg/L and transferrin saturation (Tsat) <20%, was present in 39.3% of controls and 61.4% of HF [odds ratio (OR) 3.5, 95% confidence interval (CI) 2.5-4.9, adjusting for clinical covariates]. Independent correlates of ID in HF were Indian ethnicity (OR 2.4 vs. Chinese, 95% CI 1.2-5.0), female gender (OR 2.8, 95% CI 1.7-4.8), larger body mass index (OR 1.05/unit increase, 95% CI 1.01-1.1) and decreased left ventricular ejection fraction (OR 1.03/unit decrease, 95% CI 1.01-1.04). In a subset of 48 HF patients undergoing cardiopulmonary exercise testing, Tsat correlated with peak oxygen consumption (ρ = 0.53, P < 0.01), independent of baseline characteristics. The HF patients with Tsat <20% as well as anaemia showed the poorest event-free survival after adjusting for clinical covariates. CONCLUSIONS: ID was highly prevalent and independently related to functional capacity and outcomes in our cohort. These findings suggest a pathophysiological role of ID in HF and support its importance as a therapeutic target in Southeast Asian patients with HF.

Impact Of Sex On Clinical Characteristics And In-Hospital Outcomes In A Multi-Ethnic Southeast Asian Population Of Patients Hospitalized For Acute Heart Failure.

OBJECTIVES: To study sex differences in clinical characteristics and outcomes among multi-ethnic Southeast Asian patients with hospitalized heart failure (HHF). BACKGROUND: HHF is an important public health problem affecting man and women globally. Reports from Western populations suggest striking sex differences in risk factors and outcomes in HHF. However, this has not been studied in a multi-ethnic Asian population. METHODS: Using the population-based resources of the Singapore Cardiac Data Bank, we studied 5,703 consecutive cases of HHF admitted across hospitals in the Southeast Asian nation of Singapore from 1st January, 2008 through 31st December, 2009. RESULTS: Women accounted for 46% of total admissions and were characterized by older age (73 vs. 67 years; p<0.001), higher prevalence of hypertension (78.6 vs. 72.1%; p<0.001) or atrial fibrillation (22.2 vs. 18.1%; p<0.001), and lower prevalence of coronary artery disease (33.8 vs. 41.0%; p<0.001) or prior myocardial infarction (14.9 vs. 19.8%; p<0.001). Women were more likely than men to have HHF with preserved ejection fraction (42.5% versus 20.8%, p < 0.001). Women were less likely than men to receive evidencebased therapies at discharge, both in the overall group and in the sub-group with reduced ejection fraction. Women had longer lengths of stay (5.6 vs. 5.1 days; p<0.001) but similar in-hospital mortality and one-year rehospitalization rates compared to men. Independent predictors of mortality or rehospitalization in both men and women included prior myocardial infarction and reduced ejection fraction. Among women alone, additional independent predictors were renal impairment, atrial fibrillation, and diabetes. Prescription of beta-blockers and ACE-inhibitors at discharge was associated with better outcomes. CONCLUSION: Among multi-ethnic Asian patients with HHF, there are important sex differences in clinical characteristics and prognostic factors. These data may inform sex-specific strategies to improve outcomes of HHF in Southeast Asians.

The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study: rationale and design.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. METHODS: The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. CONCLUSIONS: The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients.